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Intravenous Phenytoin Loading in Patients after Neurosurgery and in Status Epilepticus

A Population Pharmacokinetic Study

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Summary

In 49 patients treated with intravenous phenytoin after a neurosurgical procedure or because of repetitive frequent seizures, the serum concentration was measured before and 2 hours after an intravenous bolus injection. Based on these data the apparent volume of distribution and intra- and interpatient variability were determined in this representative patient population, using the statistical package NONMEM. From 5 characteristics tested (age, sex, bodyweight, serum albumin, renal function) only bodyweight was found to significantly influence the apparent volume of distribution of phenytoin. The population average was estimated as 1.0 ± 0.04 L/kg (estimate ± SE) and interindividual variability, expressed as coefficient of variation, was 23 ± 6%. By means of Monte Carlo simulations an optimal dosing scheme for phenytoin loading has been calculated. Based on these results, a dose of 15 mg/kg divided into 3 intravenous injections administered 2 hours apart at a maximum rate of 50 mg/min is recommended. This loading regimen should result in therapeutic concentrations (10 to 20 mg/L) in 90% of patients within 6 hours.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Internal Medicine and Department of Neurosurgery, University Hospital (Kantonsspital), Basel, Switzerland

    Samuel Vožeh, Toshihiko Uematsu, Leon Aarons, Pierre Maitre, Hans Landolt & Otmar Gratzl

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  1. Samuel Vožeh
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  2. Toshihiko Uematsu
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  3. Leon Aarons
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  4. Pierre Maitre
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  5. Hans Landolt
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  6. Otmar Gratzl
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Vožeh, S., Uematsu, T., Aarons, L. et al. Intravenous Phenytoin Loading in Patients after Neurosurgery and in Status Epilepticus. Clin-Pharmacokinet 14, 122–128 (1988). https://doi.org/10.2165/00003088-198814020-00004

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  • DOI: https://doi.org/10.2165/00003088-198814020-00004

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